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Clinical and genetic implications of arthrogryposis and allied disorders
ABSTRACTS OF T H E 7th ANNUAL MEETING
CONGENITAL ABNORMALITIES IN SOUTH AUSTRALIAA CLINICAL EPIDEMIOLOGICAL REVIEW AILEEN CONNONSouth Australian Health Commission, Adelaide At the conclusion of the first year of the South Australian Perinatal Statistical Collection, 647 congenital abnormalities, identified from Supplementary Birth Records and confirmed by doctors, have been analysed in relation to maternal factors and perinatal outcome. Against a background frequency of 3.4% major and minor abnormalities in South Australia, an association has been found between increased relative frequency of congenital abnormalities in relation to maternal age, previous poor obstetric history, maternal diabetes and inadequate antenatal care. The types of congenital abnormalities will be presented along with information relating to low birthweight, perinatal mortality and increased neonatal morbidity among babies born with a congenital abnormality.
STATE-WIDE CONGENITAL ABNORMALITY DATA COLLECTION South Australian Health Commission, Adelaide A ~ L E ECONNON N A State-wide congenital abnormality data collection-the process used in South Australia. 1. Preparatory consultations 2. Planning stage 3. Pilot program 4. Formal collection based on the Congenital Abnormality Form 5 . Confirmation of diagnosis 6. Data output summary.
COMPARATIVE COST OF TREATMENT AND ANTENATAL DIAGNOSTIC SERVICES FOR THALASSEMIA IN NEW SOUTH WALES J . COWAN Department of Preventive and Social Medicine, University of Svdney The majority of patients with homozygous beta thalassemia require blood transfusions every 4-5wk, and iron chelation therapy by means of subcutaneous infusion of desferrioxamine 5-6 nights a week. All antenatal diagnoses for major hemoglobinopathies in New South Wales so far have been done by fetal blood sampling, a more difficult procedure than amniocentesis. It is estimated that by 1982 almost 50% of fetuses at risk for a major hemoglobinopathy in New South Wales were tested. A study has been done to cost all treatment services during 1982 for the major hemoglobinopathies in New South Wales. This has been compared with the cost of the antenatal diagnostic services undertaken for hemoglobinopathies during that year.
THE SIGNIFICANCE OF DISEASE ASSOCIATIONS WITH SUPRATYPES, HAPLOTYPES, COMPLOTYPES AND SINGLE ALLELES R. L. DAWKINSClinical Immunology, Royal Perth Hospital, W.A. Mapping of the major histocompatibility complex (MHC) in man is now more informative since products at more than 10 loci can be detected (HLA A, B, C, DR, D, MT, MB, C4A and B, Bf, C2,21-0H). Some diseases (e.g. ankylosing spondylitis) may be associated with only one allele (e.g. 27) at one locus (HLA B) but it is now clear that it is more usual to find that disease associations involve one or more supratypes (combinations of alleles at multiple loci). Apparently, other diseases may be associated with particular haplotypes (identified by family studies), or with specific complotypes but detailed mapping has not been undertaken.
101
These observations may be explained in terms of the differing functional significance of different MHC loci including those involved in complement synthesis and steroid metabolism.
AXIAL MESODERMAL DYSPLASIA: A USEFUL UNIFYING CONCEPT IN DYSMORPHOLOGY R. J. M. GARDNERPaediatrics and Child Health, University of Otago, Dunedin, N.Z. Syndromology has largely been, of necessity, an exercise in splitting, as more and more distinct disorders come to be identified. T o bring some order to this multitude, various systems of classification have been offered. For the student of pathogenesis, classification by mechanism of developmental defect is an attractive concept. One such grouping has been proposed by Russell et al. (Pediatrics, February, 1981): a number of syndromes may have a common underlying defect in the aberrant behaviour of mesoderm arising from the primitive streak. Some (e.g. cloaca1 exstrophy) may be largely caudal; some (e.g. Goldenhar syndrome) largely rostral; and some more widespread (e.g. VATER Association). There are grounds for supposing that dysfunction of cell surface “morphogenesis proteins” may be what leads to the tissue dysplasia that in turn underlies the malformations. The distribution of the defect may reflect the timing of the gene(s) in question, and/or the field(s) of influence of the proteins(s) coded for. The basic cause could be genetic, epigenetic, or extrinsic. I have seen a baby with persistent cloaca and no caudal opening with a gross external genital deformity, and vertebral defects; and know of one other very similar case. The concept of mesodermal dysplasia has been helpful in placing this (? “new”) disorder in context, and in understanding why this particular pattern of malformation might arise.
CLINICAL AND GENETIC IMPLICATIONSOF ARTHROGRYPOSIS AND ALLIED DISORDERS G . S. GERICKE A N D P . BEICHTON MRC Unit for Inherited Skeletal Dysplasias, Department of Human Genetics, University of Cape Town, Republic of South Africa Increasing heterogeneity in multiple congenital contractural syndromes has necessitated reappraisal of accumulated patient data in the MRC Unit for Inherited Skeletal Disorders at the Department of Human Genetics, University of Cape Town. Information concerning more than 250 patients with congenital joint contractures was analysed. The nongenetic anterior horn cell type of arthrogryposis multiplex congenita (amyoplasia) accounted for approximately 20% while the remainder comprised various syndromic disorders in which rigidity of joints was a significant cmponent. Diagnostic precision is crucial in genetic counselling for congenital articular rigidities.
MULTIPLE CONGENITAL CONTRACTURES AND EARLY LETHALITY G. GERICKEAND P . BEIGHTONMRC Unit f o r Inherited Skeletal Dysplasias, Department of Human Genetics, University of Cape Town, Republic of South Africa Since no reduced life span after the first year has been described for arthrogryposis multiplex congenita (AMC), a specific type of multiple congenital contractural disorder, a study was undertaken to review whether early lethality is a component of this condition. An analysis of accumulated patient data in the MRC Unit for Inherited Skeletal Disorders, Department of Human Genetics, University of Cape Town, revealed 34 patients with multiple congenital contractures who had been
CONGENITAL ABNORMALITIES IN SOUTH AUSTRALIAA CLINICAL EPIDEMIOLOGICAL REVIEW AILEEN CONNONSouth Australian Health Commission, Adelaide At the conclusion of the first year of the South Australian Perinatal Statistical Collection, 647 congenital abnormalities, identified from Supplementary Birth Records and confirmed by doctors, have been analysed in relation to maternal factors and perinatal outcome. Against a background frequency of 3.4% major and minor abnormalities in South Australia, an association has been found between increased relative frequency of congenital abnormalities in relation to maternal age, previous poor obstetric history, maternal diabetes and inadequate antenatal care. The types of congenital abnormalities will be presented along with information relating to low birthweight, perinatal mortality and increased neonatal morbidity among babies born with a congenital abnormality.
STATE-WIDE CONGENITAL ABNORMALITY DATA COLLECTION South Australian Health Commission, Adelaide A ~ L E ECONNON N A State-wide congenital abnormality data collection-the process used in South Australia. 1. Preparatory consultations 2. Planning stage 3. Pilot program 4. Formal collection based on the Congenital Abnormality Form 5 . Confirmation of diagnosis 6. Data output summary.
COMPARATIVE COST OF TREATMENT AND ANTENATAL DIAGNOSTIC SERVICES FOR THALASSEMIA IN NEW SOUTH WALES J . COWAN Department of Preventive and Social Medicine, University of Svdney The majority of patients with homozygous beta thalassemia require blood transfusions every 4-5wk, and iron chelation therapy by means of subcutaneous infusion of desferrioxamine 5-6 nights a week. All antenatal diagnoses for major hemoglobinopathies in New South Wales so far have been done by fetal blood sampling, a more difficult procedure than amniocentesis. It is estimated that by 1982 almost 50% of fetuses at risk for a major hemoglobinopathy in New South Wales were tested. A study has been done to cost all treatment services during 1982 for the major hemoglobinopathies in New South Wales. This has been compared with the cost of the antenatal diagnostic services undertaken for hemoglobinopathies during that year.
THE SIGNIFICANCE OF DISEASE ASSOCIATIONS WITH SUPRATYPES, HAPLOTYPES, COMPLOTYPES AND SINGLE ALLELES R. L. DAWKINSClinical Immunology, Royal Perth Hospital, W.A. Mapping of the major histocompatibility complex (MHC) in man is now more informative since products at more than 10 loci can be detected (HLA A, B, C, DR, D, MT, MB, C4A and B, Bf, C2,21-0H). Some diseases (e.g. ankylosing spondylitis) may be associated with only one allele (e.g. 27) at one locus (HLA B) but it is now clear that it is more usual to find that disease associations involve one or more supratypes (combinations of alleles at multiple loci). Apparently, other diseases may be associated with particular haplotypes (identified by family studies), or with specific complotypes but detailed mapping has not been undertaken.
101
These observations may be explained in terms of the differing functional significance of different MHC loci including those involved in complement synthesis and steroid metabolism.
AXIAL MESODERMAL DYSPLASIA: A USEFUL UNIFYING CONCEPT IN DYSMORPHOLOGY R. J. M. GARDNERPaediatrics and Child Health, University of Otago, Dunedin, N.Z. Syndromology has largely been, of necessity, an exercise in splitting, as more and more distinct disorders come to be identified. T o bring some order to this multitude, various systems of classification have been offered. For the student of pathogenesis, classification by mechanism of developmental defect is an attractive concept. One such grouping has been proposed by Russell et al. (Pediatrics, February, 1981): a number of syndromes may have a common underlying defect in the aberrant behaviour of mesoderm arising from the primitive streak. Some (e.g. cloaca1 exstrophy) may be largely caudal; some (e.g. Goldenhar syndrome) largely rostral; and some more widespread (e.g. VATER Association). There are grounds for supposing that dysfunction of cell surface “morphogenesis proteins” may be what leads to the tissue dysplasia that in turn underlies the malformations. The distribution of the defect may reflect the timing of the gene(s) in question, and/or the field(s) of influence of the proteins(s) coded for. The basic cause could be genetic, epigenetic, or extrinsic. I have seen a baby with persistent cloaca and no caudal opening with a gross external genital deformity, and vertebral defects; and know of one other very similar case. The concept of mesodermal dysplasia has been helpful in placing this (? “new”) disorder in context, and in understanding why this particular pattern of malformation might arise.
CLINICAL AND GENETIC IMPLICATIONSOF ARTHROGRYPOSIS AND ALLIED DISORDERS G . S. GERICKE A N D P . BEICHTON MRC Unit for Inherited Skeletal Dysplasias, Department of Human Genetics, University of Cape Town, Republic of South Africa Increasing heterogeneity in multiple congenital contractural syndromes has necessitated reappraisal of accumulated patient data in the MRC Unit for Inherited Skeletal Disorders at the Department of Human Genetics, University of Cape Town. Information concerning more than 250 patients with congenital joint contractures was analysed. The nongenetic anterior horn cell type of arthrogryposis multiplex congenita (amyoplasia) accounted for approximately 20% while the remainder comprised various syndromic disorders in which rigidity of joints was a significant cmponent. Diagnostic precision is crucial in genetic counselling for congenital articular rigidities.
MULTIPLE CONGENITAL CONTRACTURES AND EARLY LETHALITY G. GERICKEAND P . BEIGHTONMRC Unit f o r Inherited Skeletal Dysplasias, Department of Human Genetics, University of Cape Town, Republic of South Africa Since no reduced life span after the first year has been described for arthrogryposis multiplex congenita (AMC), a specific type of multiple congenital contractural disorder, a study was undertaken to review whether early lethality is a component of this condition. An analysis of accumulated patient data in the MRC Unit for Inherited Skeletal Disorders, Department of Human Genetics, University of Cape Town, revealed 34 patients with multiple congenital contractures who had been